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Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr -encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements. [Display omitted] • The pbr operon varies among diverse bacteria and mediates the detoxification of lead (Pb). • Bacterial biosensors harboring artificial pbr operon can sense bioavailable Pb(II). • Designed bacteria employing members of the pbr operon are powerful in Pb(II) biosorption. • Synthetic bacteria based on natural pbr operons have been emerging to tackle Pb pollution. [ABSTRACT FROM AUTHOR]

Two metal-organic frameworks (MOFs), namely {[Zn 3 (L) 2 (4,4′-bipy)(DMF) 2 ]·2H 2 O} n (1) and {[Cd 3 (L) 2 (4,4′-bipy)(H 2 O) 2 ].2DMF} n (2) (4,4′-bipy = 4,4′-bipyridine, DMF = N , N -dimethylformamide), were solvothermally prepared based on a rigid tricarboxylic acid 3-(3,5-dicarboxylphenyl)-5-(3-carboxylphenyl)-1-H-1,2,4-triazole (H 3 L). X-ray crystallographic analysis reveals that 1 and 2 are isostructural and both emit blue light. Notably, 1 exhibits good luminescent sensing for nitro-containing compounds and Fe 3+ ions. In addition, the emission colors of 1 can be tuned from yellow to white and to blue by encapsulating different mole ratios of Eu 3+ and Tb 3+ ions and changing the excitation wavelength. A white emission with the Commission International de l’Eclairage (CIE) coordinates of (0.331, 0.337), which fall within the white-light region, emerges upon excitation at 340 nm. [ABSTRACT FROM AUTHOR]

With the increase in cadmium (Cd) release into the environment, it is necessary to find appropriate solutions to reduce soil Cd pollution. Microorganisms are a green and effective means for the remediation of Cd-contaminated soil. In this study, in a Cd-contaminated farmland, we screened and identified novel Cd-resistant strains, Paenarthrobactor nitroguajacolicus , Lysinibacillus fusiformis , Bacillus licheniformis , and Methyllobacium brachiatum , with minimum inhibitory concentrations of 100, 100, 50, and 50 mg/L, respectively, and added them each to pots containing Cd-contaminated rape plants to explore their remediation ability. The results showed that treatment with each of the four strains significantly increased the abundance of Nitrospirae , Firmicutes , Verrucomicrobia , and Patescibacterium in the rhizosphere soil of the plants. This led to changes in soil physical and chemical indices; pH; and available phosphorus, urease, and catalase activities, which were significantly negatively correlated with bioavailable Cd, reducing 28.74–58.82 % Cd enrichment to plants and 23.72–43.79 % Cd transport within plants, and reducing 5.52–10.68 % available cadmium in soil, effectively reducing the biotoxicity of Cd. Thus, this study suggests microbial remediation as a reliable option, forming a basis for the remediation of Cd-contaminated soil. [Display omitted] • Four new strains screened have good Cd tolerance and removal efficiency. • Cd significantly altered morphology and extracellular bonds/functional groups of the strains. • The strains increased the abundance of Nitrospirae , Firmicutes , and Verrucomicrobia in soil. • The strains increased soil pH, urease, alkaline phosphatase and catalase enzyme activities. • The strains treatment significantly decreased soil bioeffective Cd content and crop Cd content. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) pollution in crops seriously affects the ecosystem and human health. Effective measures should be employed to reduce the absorption and accumulation of cadmium in crops. Currently, there are many pieces of research on the application of biochar (BC) and selenium (Se) alone to the remediation of soil Cd pollution; however, few investigations have been devoted to the application of BC and Se together to the remediation of soil Cd pollution. The peanut was taken as the target crop to explore the effects of exogenous selenium and biochar on the remediation of soil Cd pollution. The response of the soil bacterial community to two levels of Cd concentration and its relationship with soil properties and Cd availability are methodically investigated. This study sets two cadmium pollution concentrations of low Cd (5 mg/ kg) and high Cd (20 mg/kg), as well as six treatments: blank, BC, soil Se, soil Se-BC, leaf Se, and leaf Se-BC. The achieved results revealed that both Se and BC could noticeably enhance the yield of peanut seeds and reduce the Cd content in peanut seeds. Among them, Se-BC treatment on soil exhibits the most influence, which reduces the Cd content by 47.86%. Se and BC also affect the physical and chemical properties of soil and remarkably magnify the content of soil available phosphorus, organic matter, soil pH, and soil conductivity. For instance, then effect is detected in the case of applying selenium biochar to soil, leading to an increase of about 64.38%, 72.62%, 2.64%, and 61.15%, respectively, and reducing the content of soil available cadmium by 21.02%. Redundancy analysis confirms that these properties enhance the abundance of dominant bacteria Actinobacteria , Proteobacteria, and Chloroflexi. The correlation analysis also indicates that Saccharimonadales , Bacillus , Arthrobacter , and other bacteria with the function of reducing the bioavailability of cadmium in soil reveal a considerable positive correlation with the variations of physical and chemical properties. In general, exogenous Se and BC incorporate to drop the content of available Cd in the soil through direct passivation, passivation caused by soil environmental change, and passivation caused by altering the soil microbial community structure; as a result, the migration and enrichment of Cd in peanut seeds are blocked and reduced. Moreover, the mixed application of BC and soil Se exhibits the best effect. • Underlow cadmium stress, foliar application of selenium was the most effective,reducing 35.65% of soil available cadmium. • Underhigh cadmium stress, a mixture of biochar and soil application of selenium wasthe most effective, reducing 47.87% of soil available cadmium. • Seleniumand biochar encouraged the growth of Saccharimonadales, Arthrobacter,and Bacillus, all of which help to reduce soil cadmium toxicity. [ABSTRACT FROM AUTHOR]

Word embedding is a basic task in natural language processing area. Unlike English, Chinese subword units, such as characters, radicals, and components, contain rich semantic information which can be used to enhance word embeddings. However, existing methods neglect the semantic contribution of corresponding subword units to the word. In this work, we employ attention mechanism to capture the semantic structure of Chinese words and propose a novel framework, named Attention-based multi-Layer Word Embedding model(ALWE). We also design an asynchronous strategy for updating embedding and attention efficiently. Our model learns to share subword information between distinct words selectively and adaptively. Experimental results on the word similarity, word analogy, and text classification show that the proposed model outperforms all baselines, especially when words do not appear frequently. Qualitative analysis further demonstrates the superiority of ALWE. [ABSTRACT FROM AUTHOR]

[Display omitted] • The development of a crystallization inhibition strategy led to a dense copper phyllosilicate precursor. • Significantly higher oxygen vacancy concentration was found on the surface of the reduced sample Cu/SiO 2 (20 K) than traditional Cu/SiO 2. • Cu/SiO 2 (20 K) showed prominent activity in methanol dehydrogenation coupled with DMO hydrogenation reactions, with a high yield of 85.4% of ethylene glycol (EG) achieved. • DFT calculations were performed to elucidate the intrinsic active site during reaction over Cu/SiO 2 (20 K). The reducibility of heterogeneous Cu-based precursor greatly influences the activity and stability of the final catalysts because the excessive reduction to metallic Cu significantly deactivates the catalysts. Herein, we develop a crystallization inhibition strategy to fabricate the granular and densely stacked copper phyllosilicate precursor which possesses stronger resistance to H 2 reduction. The reduction-resistant CuSiO 3 precursor contains more abundant Cu+ species and oxygen deficiencies, which was verified by O 2 -TPD, TGA, O XPS and Cu XAES measurements, and is beneficial for methanol dehydrogenation and dimethyl oxalate (DMO) adsorption. A high yield of 85.4% of ethylene glycol (EG) was achieved from DMO hydrogenation at 240 °C, with methanol as both the solvent and hydrogen supplier. The delicately designed synthesis of specific Cu precursor with unique properties resulted in an excellent multi-functional Cu catalyst for coupled methanol dehydrogenation and DMO hydrogenation to EG. [ABSTRACT FROM AUTHOR]

Antiepileptic drugs (AEDs) are the first choice in magnetic resonance imaging (MRI)-negative patients with epilepsy, although the responses to AEDs are diverse. Preoperative evaluation and postoperative prognosis in MRI-negative epilepsy have been reported. However, there are few tools for predicting the response to AEDs. Herein, we developed an AED response scale based on clinical factors and video-electroencephalography (VEEG) in MRI-negative patients with epilepsy. A total of 132 consecutive patients with MRI-negative epilepsy at the Epilepsy Center of Henan Provincial People's Hospital between August 2016 and August 2018 were included. Patients were further divided into drug-responsive epilepsy ([DSE-MRI (−)]; n = 101) and drug-resistant epilepsy ([DRE-MRI (−)]; n = 31) groups. The clinical and VEEG factors were evaluated in univariate analyses and multivariate logistic regression analyses. A scale was derived and the scores categorized into 3 risk levels of DRE-MRI (−). A scale was established based on 4 independent risk factors for DRE-MRI (−). The scale had a sensitivity of 83.87%, specificity of 80.20%, positive likelihood ratio of 4.24, negative likelihood ratio of 0.20, and showed good discrimination with the area under the curve (AUC) of 0.886 (0.826–0.946). The categorization of the risk score based on this scale was: low risk (0–3 points), medium risk (3–5 points), and high risk (> 5 points). We established a DRE-MRI (−) scale with a good sensitivity and specificity, which may be useful for clinicians when making medical decisions in patients with MRI-negative epilepsy. • AEDs are the first choice in MRI-negative epilepsy patients. • A scale was established based on clinical factors and VEEG, which showed a good discrimination and may be useful for making medical decisions in patients with MRI-negative epilepsy. • The risk lever was categorized as low risk (0–3 points), medium risk (3–5 points), and high risk (> 5 points) [ABSTRACT FROM AUTHOR]

Abstract Objective The objective of this study was to assess the anxiety and depression of caregivers of adult patients with epilepsy (PWE) and evaluate its effect on patient quality of life (QOL). Method One hundred sixty pairs of adult PWE and their caregivers were enrolled in our study. Quality of life in adult PWE was evaluated with the Quality of Life in Epilepsy Inventory-31 scale (QOLIE-31). Symptoms of anxiety and depression in caregivers were assessed with the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) respectively. Correlation and stepwise multiple liner regression analyses were used as statistical analysis. Results Of the caregivers, 41 (31.30%) had anxiety symptoms (HAM-A scores > 6) and 44 (33.59%) had depression symptoms (HAM-D scores > 6). Caregiver anxiety was significantly associated with poorer adult PWE QOL scores in four of the seven subscales and the QOLIE-31 total score. Caregiver depression was significantly associated with poorer adult PWE QOL in all seven subscales as well as the QOLIE-31 total score. Caregiver depression was an independent predictor of the QOLIE-31 total score and five subscales: seizure worry, emotional wellbeing, energy/fatigue, cognitive, and medication effects. Conclusion Caregivers of adult PWE are at high risk of experiencing anxiety and depression. Caregiver psychological status, especially depression, was an independent predictor of poorer QOL for adult PWE. Highlights • Caregivers of adult PWE are at high risk of experiencing anxiety and depression. • Caregiver depression was an independent predictor of poorer QOL for adult PWE. • Older age at seizure onset and being with a female caregiver have association with better QOL in adult PWE. • The number of AEDs and relationship to patients have no significant association with adult PWE QOL. [ABSTRACT FROM AUTHOR]

Abstract A three-dimensional (3D) zinc metal-organic framework (MOF), {[Zn 2 (μ 3 -OH)(cpta)(4,4′-bipy)]·H 2 O} n (1) (4,4′-bipy = 4,4′-bipyridine) was solvothermally synthesized base on a semirigid V-shaped multicarboxylate ligand 2–4(-carboxyphenoxy)terephthalic acid (H 3 cpta). 1 has a complicated 3D structure in which the tetramer [Zn 4 (μ 3 -O) 2 O 10 N 4 ] second building units (SBUs) are interconnected by the V-shaped cpta3− and 4,4′-bipy ligands. 1 shows good selective and sensitive fluorescence sensing effect for detecting Cr(III)/Cr(VI) ions and p -nitrotolune (p -NP). The detection limits of Cr3+, Cr 2 O 7 2−, and p -NP can reach 5.55 × 10−6, 6.91 × 10−6 and 4.01 × 10−6 M, respectively. Moreover, 1 can be recycled at least four times for sensing Cr3+ and Cr 2 O 7 2− ions. In addition, the luminescence intensity of 1 is strongly correlated with the pH value in a pH range from 2 to 12. Graphical abstract A three-dimensional (3D) zinc metal-organic framework (MOF) was synthesized under solvothermal condition by the assembly of semirigid V-shaped multicarboxylate ligand 2–4(-carboxyphenoxy)terephthalic acid (H 3 cpta) and 4,4′-bipyridine (4,4′-bipy) with Zn(II) ion. 1 shows good selective fluorescence sensing for detecting Cr(III)/Cr(VI) ions and p -nitrotolune (p -NP). fx1 Highlights • A 3D Zn-MOF has been successfully synthesized. • It exhibits highly luminescent sensing properties for Cr3+, Cr 2 O 7 2−, p -NP and pH. • The detection limits of Cr3+, Cr 2 O 7 2−, and p -NP can reach 5.55 × 10−6, 6.91 × 10−6 and 4.01 × 10−6 M, respectively. • It can be recycled at least four times for sensing Cr3+ and Cr 2 O 7 2− ions. [ABSTRACT FROM AUTHOR]

Objectives Many studies have reported the increased presence of gastrointestinal (GI) symptoms in children with autism spectrum disorders (ASD). Altered microbiome profiles, pro-inflammatory responses and impaired intestinal permeability have been observed in children with ASD and co-morbid GI symptoms, yet few studies have compared these findings to ASD children without GI issues or similarly aged typical developing children. The aim of this study was to determine whether there are biological signatures in terms of immune dysfunction and microbiota composition in children with ASD with GI symptoms. Methods Children were enrolled in one of four groups: ASD and GI symptoms of irregular bowel habits (ASD GI ), children with ASD but without current or previous GI symptoms (ASD NoGI ), typically developing children with GI symptoms (TD GI ) and typically developing children without current or previous GI symptoms (TD NoGI ). Peripheral blood mononuclear cells (PBMC) were isolated from the blood, stimulated and assessed for cytokine production, while stool samples were analyzed for microbial composition. Results Following Toll-Like receptor (TLR)-4 stimulation, the ASD GI group produced increased levels of mucosa-relevant cytokines including IL-5, IL-15 and IL-17 compared to ASD NoGI . The production of the regulatory cytokine TGFβ1 was decreased in the ASD GI group compared with both the ASD NoGI and TD NoGI groups. Analysis of the microbiome at the family level revealed differences in microbiome composition between ASD and TD children with GI symptoms; furthermore, a predictive metagenome functional content analysis revealed that pathways were differentially represented between ASD and TD subjects, independently of the presence of GI symptoms. The ASD GI also showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability, compared to the other groups. Conclusions Overall our findings suggest that children with ASD who experience GI symptoms have an imbalance in their immune response, possibly influenced by or influencing metagenomic changes, and may have a propensity to impaired gut barrier function which may contribute to their symptoms and clinical outcome. [ABSTRACT FROM AUTHOR]

Two zinc(II) coordination polymers (CPs), namely, {[Zn 2 (µ 5 -tzbt)(µ-trz)]·3.5H 2 O} n (trz = 1,2,4-triazolate) (1) and {[Zn 2 (µ 5 -tzbt)(µ-OH)(phen)]·4H 2 O} n (phen = 1,10-phenanthroline) (2) have been constructed from 1-(triazol-1-yl)-2,4,6-benzene tricarboxylic acid (H 3 tzbt) under hydrothermal conditions. Single crystal X-ray diffraction analysis reveals that 1 displays 3D framework containing left - handed and right - handed helical chains, whilst 2 is a 2D layered structure. These new CPs both exhibit intensive fluorescence emission at room temperature. Notably, they perform as host for the encapsulation of Ln(III) ions and serve as an antenna to sensitize Tb(III) ions. By encapsulating different Ln(III) ions, both Eu 0.2 Tb 0.8 @ 1 and Eu 3+ @ 2 present white-light emission. In addition, 2 exhibits highly luminescent sensing properties for acetone. [ABSTRACT FROM AUTHOR]

Dam damming has an adverse effect on river connectivity, leading to downstream nutrient transport and ecosystem fragmentation. Dam demolition has already been used as an effective measurement to promote the ecological restoration of rivers. Few studies have analyzed the short-term variations of water quality following dam removal. This study investigated the response of multi-element and multi-form water quality parameters, such as water temperature (TEM), dissolved oxygen (DO), pH, biochemical oxygen demand (BOD 5), chemical oxygen demand (COD), ammonia nitrogen (NH 3 –N), total nitrogen (TN) and total phosphorus (TP), to the demolition of 4 dams in Chishui River Basin in short term. The study employed Spearman correlation analysis and Generalized Additive Models to identify the critical variables and examine the inter-relationship between these water quality parameters. Our results show that COD, BOD 5, and TP increased after two weeks of dam removal, while NH 3 –N and TN decreased. Dams with larger volumes and higher heights led to more obvious deterioration for DO, COD, and BOD 5. We also found that denitrification and resuspension dominantly affect the water quality indicators following dam removal. Denitrification is responsible for downstream TN increase, and resuspension and related sediment transport contribute to downstream TP increase. Our study provides an opportunity to explore the transformation and migration of N and P in reservoirs following dam removal in the short term and presents a scientific basis and new thought for the short-term protection and management following the clean-up and rectification of multiple small hydropower plants. • COD, BOD 5 , and TP are short-term risk factors following dam removal. • TN and NH 3 –N decreased after two weeks of dam removal. • Dam removal altered correlations among water parameters. • Larger reservoirs and higher dams led to greater water quality decline. • The N retention is the mainly reason for the TN concentration decrease. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Background: Smad3 is a principal intracellular mediator of signaling for transforming growth factor β, a cytokine involved in pleiotropic pathophysiological processes including inflammation and immunity. The function of Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic shock has not been characterized. Methods: Smad3−/−(referred hereafter as KO) and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma levels of nitrite were measured. The iNOS messenger RNA and protein levels in lung, kidney, and spleen were also analyzed. Results: Mice lacking functional Smad3 respond to LPS with greater mortality than their WT littermates. The high mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite during the experimental period; however, LPS administration caused more dramatic changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein levels in lung, kidney, and spleen were more strongly increased in KO mice than in WT mice after LPS administration. Conclusions: Defects in the Smad3 gene may increase susceptibility to the development of septic hypotension because of enhanced iNOS production. [Copyright &y& Elsevier]

Abstract: Background: The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. Materials and methods: C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1β) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. Results: p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1β mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. Conclusions: p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver. [Copyright &y& Elsevier]

Background: Splanchnic ischemia is common in critically ill patients, and it can result in injury not only of the intestine but also in distant organs, particularly in the lung. Local inflammatory changes play a pivotal role in the development of acute lung injury after intestinal ischemia, but the underlying molecular mechanisms are not fully understood. We sought to examine the role of Toll-like receptor 4 (TLR4) in the mouse model of intestinal ischemia-reperfusion (I/R)-induced lung injury and inflammation. Materials and Methods: Adult male TLR4 mutant (C3H/HeJ) mice and TLR4 wild-type (WT) (C3H/HeOuJ) mice were subjected to 40 min of intestinal ischemia by clamping the superior mesenteric artery followed by 6 h of reperfusion. Lung histology was assessed and parameters of pulmonary microvascular permeability, inflammatory cytokine expression, and neutrophil infiltration were measured. Activation of mitogen-activated protein kinases (MAPKs) and the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1) in the lungs were also detected. Results: After intestinal I/R, lungs from TLR4 mutant mice demonstrated a significantly lower histological injury, a marked reduction of epithelial apoptosis associated with the decreased level of cleaved caspase-3 and the increased ratio of Bcl-xL to Bax proteins, and a large reduction in pulmonary vascular permeability and myeloperoxidase (MPO) activity in comparison with WT mice. TLR4 mutant mice also displayed marked decreases in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) expression. Following intestinal I/R, phosporylation of p38 MAPK and activation of NF-κB and AP-1 were significantly inhibited in lung tissue from TLR4 mutant mice compared with WT controls. Conclusions: These data suggest that TLR4 plays an important role in the pathogenesis of intestinal I/R-induced acute lung injury and inflammation and that p38 kinase and NF-κB may be involved in TLR4 signaling-mediated lung inflammatory processes during intestinal I/R. [Copyright &y& Elsevier]

Abstract: Angiotensin II is able to trigger inflammatory responses through an angiotensin II type 1 (AT1) receptor. The role of AT1 receptor in acute lung injury (ALI) is poorly understood. Mice were randomly divided into three groups (n =40 each groups): NS group; LPS group (2mg/kg LPS intratracheally); and LPS+ZD 7155 group, 10mg/kg ZD 7155 (an AT1 receptor antagonist) intraperitoneally 30min prior to LPS exposure. Samples from the lung were isolated and assayed for histopathology analyses or proinflammatory gene expressions, angiotensin II receptors expressions and nuclear factors activities. LPS exposure resulted in severe ALI, elevated levels of TNF-α and IL-1β mRNA expressions, and increased activities of NF-κB and activated protein (AP)-1. Upregulation of AT1 receptor and down-regulation of AT2 receptor were also observed after LPS challenge. Pretreatment with ZD 7155 significantly inhibited the increase of AT1 receptor expression and upregulated AT2 receptor expression. ZD 7155 also reduced the mRNA expression of TNF-α and IL-1β, inhibited the activation of NF-κB and AP-1, and improved lung histopathology. These findings suggest that antagonism of AT1 receptor inhibits the activation of NF-κB and AP-1 in the lung, which may mediate the release of TNF-α and IL-1β and contribute to LPS-induced ALI. [Copyright &y& Elsevier]

Abstract: Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-β1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-β1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-β1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-β1 signaling pathway. [Copyright &y& Elsevier]